Multifactorial diseases result from complex interactions between a number of predisposing factors, including genotypes at one or more loci and a variety of environmental exposures that trigger, accelerate or exacerbate the disease process. One approach to the identification of the gene loci involved in a complex disorder is to examine the involvement of a candidate gene - identified due to its physiologic role or its causal role in a monogenic disorder of a similar phenotype - by genotyping for polymorphisms within the gene and performing association studies. Chronic recurrent multifocal osteomyelitis (CRMO) associated with congenital dyserythropoietic anemia (CDA) and an inflammatory dermatosis is a complex childhood syndrome with autosomal recessive inheritance (Majeed syndrome). The inflammatory dermatoses in Majeed syndrome are Sweet syndrome in affected individuals and psoriasis in some carriers. More frequently, CRMO, CDA, Sweet syndrome and psoriasis occur independent of each other as isolated entities posing as multifactorial "complex" disorders. We have shown that homozygous mutations in LPIN2 are responsible for Majeed syndrome in two unrelated families. Furthermore, LPIN2 is located within a psoriasis susceptibility locus. We hypothesize that LPIN2 is the gene that predisposes to psoriasis in this locus. We also hypothesize that LPIN2 variations play a role in the genetic etiology of the non-syndromic CRMO. We are proposing to examine these hypotheses by performing association studies with markers within the LPIN2 gene on two cohorts of patients with psoriasis and a cohort of patients with CRMO and their parents. The association studies will be followed by sequencing to identify LPIN2 variantions and by techniques to detect large deletions or duplications within the genomic structure of LPIN2. The long term objective is to identify the mechanism and biologic pathway of bone and skin inflammation to lay the background for the development of pathogenesis oriented and targeted biologic or chemical therapy. The goal of this project is to determine whether the gene, LPIN2, which is responsible for a rare genetic disorder of bone and skin inflammation is one of the genes that predispose to psoriasis. It also examines whether LPIN2 can be a cause of chronic recurrent multifocal osteomyelitis (CRMO). Understanding the mechanisms behind psoriasis and CRMO is very important for the development of appropriate therapy. [unreadable] [unreadable] [unreadable]